Bone mass effects of a Smad6 gene polymorphism in Japanese postmenopausal women.

Smad6 plays pivotal roles in the negative regulation of transforming growth factor beta (TGFbeta) family signaling as one of the feedback molecules. Here, we analyzed whether the human Smad6 gene is involved in the regulation of bone mass, using association analysis between bone mineral density (BMD) and single-nucleotide polymorphism (SNP) in the Smad6 gene. Association of an SNP at IVS3+26115A>C (intron 3, rs755451) in the Smad6 gene with BMD was examined in 721 Japanese postmenopausal Japanese women (age 65.2 +/- 9.6 years; mean +/- SD). The subjects bearing at least one variant C allele (CC +/- AC; n = 387) had significantly lower Z-scores for total body and lumbar BMD than the subjects with no C allele (AA; n = 334) (total body, 0.23 +/- 0.98 versus 0.50 +/- 1.07; P = 0.0004; lumbar spine, -0.20 +/- 1.38 versus 0.10 +/- 1.48; P = 0.0050). These findings suggest that the Smad6 gene is a candidate for the genetic determinants of BMD in postmenopausal women, and this SNP could be useful as a genetic marker for predicting the risk of osteoporosis.